Food allergy affects nearly 10% of all individuals. The estimated prevalence is 8% in the pediatric population and 2% in the adult population. Food allergy can be life-threatening; the primary therapy is avoidance of the allergenic food. Although the factors important in the pathogenesis of food allergy are not known, there is a genetic predisposition.
Class II HLA genotypes and a slow acetylation genetic variant of N-acetyltransferase 2 are associated with food allergy. Because food allergy occurs with higher frequency in individuals with other atopic disorders, including atopic dermatitis, asthma, and allergic rhinitis, some genes associated with atopy may be relevant in food allergy.
Interleukin (IL)-4 and IL-13 are Th2 cytokines that are critical for the development of allergic inflammation and have also been implicated in food allergy. IL-4 and IL-13 exert their effect through a common receptor, IL-4 receptor alpha (IL-4Rα). Genetic variants (polymorphisms) of IL-13, IL-4Rα, and CD14 have been implicated as atopy susceptibility genes. T cell clones specific to ovomucoid derived from egg-allergic subjects consistently expressed IL-5, IL-4, and IL-13. Patients with active atopic dermatitis and egg sensitivity had a marked increase in IL-4 synthesis by peripheral blood lymphocytes following in vitro stimulation with ovalbumin. Cells from patients with atopic dermatitis in remission had decreased IL-4 synthesis, comparable to that seen in normal individuals. Peripheral blood mononuclear cells from patients with food allergy had significantly increased IL-4 production following food challenge compared with IL-4 production prior to challenge.
CD 14 is a pattern recognition receptor that binds lipopolysaccharide (LPS) and other bacterial components. LPS binding to CD 14 activates antigen presenting cells, including macrophages and dendrtic cells, and subsequently releases proinflammatory cytokines and mediators. The gene for CD14 has been reported to contain several polymorphisms in its coding and promoter regions. One polymorphism, a C to T transition at position -159 (-159 C→T), has been shown to associate with atopy, but another study found no association of this CD 14 single nucleotide polymorphism (SNP) with asthma, atopic dermatitis, allergic rhinitis, total or specific IgE levels. The T allele, and particularly the TT genotype of the CD14-159 C→T polymorphism, is associated with food allergy.
Despite the similarities of food allergy with other atopic disorders, several characteristics of food allergy are distinct. Food allergy often presents very early in life, during the first few days or weeks while IgE responses are still immature. Thus, unlike other atopic disorders, food allergy is likely to be less dependent on mechanisms involving IgE. While sensitization to environmental allergens requires previous exposure of at least several years, sensitization to food allergens may occur after only one exposure or even in the absence of previous exposure. The early onset of food allergy indicates a role for innate immunity in its development.
Food challenge remains the gold standard for diagnosing food allergies, but has serious risks and potential complications. Additional alternative methods of determining a patient's propensity to food allergens are thus desirable.